The purpose of this Funding Opportunity Announcement (FOA)
is to advance research on male-females differences in drug and alcohol abuse
and addiction and on factors specific to women. Both human and animal
model studies are sought.

Key Dates

Posted Date

December 12, 2013

Open Date (Earliest Submission Date)

January 16, 2014

Letter of Intent Due Date(s)

Not Applicable

Application Due Date(s)

Standard dates apply, by 5:00 PM
local time of applicant organization.

Applicants are encouraged to apply early to allow adequate
time to make any corrections to errors found in the application during the
submission process by the due date.

It is critical that applicants follow the instructions in
the SF424
(R&R) Application Guide, except where instructed to do otherwise (in
this FOA or in a Notice from the NIH Guide for Grants and Contracts).
Conformance to all requirements (both in the Application Guide and the FOA)
is required and strictly enforced. Applicants must read and follow all
application instructions in the Application Guide as well as any
program-specific instructions noted in Section
IV. When the program-specific instructions deviate from those in the
Application Guide, follow the program-specific instructions. Applications that
do not comply with these instructions may be delayed or not accepted for review.

There are several options to submit your application to the agency through Grants.gov. You can use the ASSIST system to prepare, submit and track your application online. You can download an application package from Grants.gov, complete the forms offline, submit the completed forms to Grants.gov and track your application in eRA Commons. Or, you can use other institutional system-to-system solutions to prepare and submit your application to Grants.gov and track your application in eRA Commons. Learn more.

In order to enhance the growth and
evolution of research on women and sex/gender differences, this R21 activity
code is intended to encourage new exploratory and developmental research projects
that reflect new ideas, techniques, methodologies, scientific areas and points
of that may differ substantially from current thinking or practice and may not
yet be supported by substantial preliminary data. Projects could include the
unique and innovative use of an existing methodology. Studies may involve
considerable risk but may lead to a breakthrough or have a major impact on our
understanding of male-female differences in drug and alcohol abuse and topics
specific to women. Preliminary data are not required for R21 applications;
however, they may be included if available.

Historically, in drug and alcohol abuse research, as in other
fields of public health research, participants were largely male.
Research findings that have emerged for over the past two decades, however,
have clearly established the importance of studying factors specific to women
and differences between males and females in all areas of drug and alcohol
abuse research. From basic studies of molecular genetics and neurotransmitter
systems to studies of epidemiology, etiology, consequences and
prevention/treatment interventions and services, the scientific and clinical
importance of analyzing data separately for males and females is becoming more
and more evident. Not only are growing numbers of studies reporting
outcomes that are specifi­c to either males or females, outcomes that are
opposite in males and females also are often found. These findings reveal
that failure to analyze data separately for males and females can lead to
incorrect conclusions regarding males or females or both.

Accumulating epidemiological and clinical research indicates
that the predictors of drug and alcohol use, abuse, and dependence often differ
in males and females. Among them are psychiatric co-morbidities, physical
and sexual abuse, trauma, prenatal drug exposure and family dysfunction.
Some predictors are gender-sensitive; that is, they are stronger for either
males or females. Others are gender-specific; that is, they apply only to
males or to females. And others are opposite in males and females.
The implications of these types of gender-based differences in risk factors remain
largely unexplored; however, they raise the possibility that interventions that
target gender-based risk factors and are guided by male-female differences in
social, cognitive and emotional development could improve outcomes for both
males and females.

Animal and human laboratory research has shown that males
and females often differ in their behavioral and biological responses to drugs.
Animal studies, for example, have found male-female differences in the
motor-activating effects of stimulants, speed of acquisition of drug
self-administration, the amount of drug self-administered, the percentage of
subjects that acquire self-administration, escalation of drug
self-administration, motivation for self-administration, and the tendency to
relapse following drug cessation. Further, factors that affect those outcomes
often do so differently in males and females. Human and animal pharmacokinetic
studies often report male and female differences, as do studies of adverse
effects of abused drugs. Both human and animal studies have established that
the menstrual/estrous cycle is a determinant of drug action, both
pharmacokinetic and behavioral. Growing numbers of brain-imagining studies are
reporting male-female differences. Despite the important progress made in
laboratory sex/gender-based research, it is in an early stage and most
researchers fail to analyze their data by sex/gender.

Numerous male-female differences in cigarette smoking and
nicotine dependence have been reported, including differences in use patterns
and dependence susceptibility, cessation rates and relapse rates, effectiveness
of nicotine replacement therapies and other pharmacotherapies, the role of
non-nicotine factors, nicotine metabolism, and pharmacogenetics. Indeed,
research on male-female differences in nicotine dependence has exceeded that of
other drugs of abuse and thus may serve to guide research on other abused
drugs. Nevertheless, many gaps remain in our understanding of male-female
differences in the nature of nicotine addiction and its prevention and
treatment, including factors specific to females such as the menstrual cycle,
pregnancy, menopause status, weight control concerns and other barriers to
cessation.

Male-female differences have been identified in various
aspects of drug abuse treatment and services research including barriers to
treatment, treatment entry characteristics, treatment and services needs, and
predictors of treatment engagement, retention, and outcomes. Research often
finds that treatments are not equally efficacious in males and females. These
male-female differences in treatment research, along with research showing
male-female differences in the determinants and predictors of drug abuse, raise
the possibility that even when treatments are shown to be equally effective for
males and females, outcomes could be improved by the addition of gender-based
approaches that are informed by this growing body of research.

According to 2010 HIV/AIDS surveillance data from the
Centers for Disease Control and Prevention

among persons living in the U.S with a diagnosis of HIV
infection at the end of 2010, injection drug use (IDU) was associated with a
greater percentage of cases among women than among men (http://www.cdc.gov/hiv/surveillance/resources/reports/2010report/pdf/2010_HIV_Surveillance_Report_vol_22.pdf).
The HIV/AIDS disease process has been found to differ between males and females;
for example, an HIV-infected woman with half the amount of virus circulating in
the bloodstream as an infected man will progress to a diagnosis of AIDS in
about the same time as the man despite comparable immune parameters (e.g., CD4
counts). Additionally, there is evidence that neurocognitive measures may
differ between HIV+ drug using males and females and that they may be
differentially impacted by HIV risk reduction interventions. Although drug
abuse plays a greater role in HIV among women than men, major gaps remain in
knowledge regarding male-female differences in the role of drug abuse in
HIV/AIDS, including the unique needs of women and how to address them in
prevention and treatment efforts.

The extant literature on male-female differences in drug
abuse strongly suggests that males and females are likely to differ in many
aspects of drug abuse yet to be explored and that in the long run, identifying
and understanding such differences can improve our understanding of the nature
and etiology of drug abuse and have implications for tailoring prevention and
treatment interventions to maximize outcomes for both males and females.
Although progress has been made in our knowledge of male-female differences in
drug abuse and issues unique to women, many gaps remain. Often studies fail to
include sex/gender analyses, and only a very small proportion of animal studies
includes female subjects thus providing no opportunity to analyze data for sex
differences and therefore running the risk that knowledge gained from animal
models of drug abuse is limited to males. Thus, in all areas of drug
abuse, research is needed that examines male-female differences and factors
specific to females.

Terminology: In scientific literature on differences between males and females, the terms
sex and gender are sometimes used interchangeably. However, they have very
different meaning as described in the 2001 IOM report, Exploring the Biological
Contributions to Human Health: Does Sex Matter? (http://lab.nap.edu/openbook.php?isbn=0309072816&page=1,
page 1), wherein sex is defined as “the classification of living things,
generally as male or female according to their reproductive organs and
functions assigned by their chromosomal complement, and gender as a person’s
self-representation as male or female, or how that person is responded to by
social institutions on the basis of the individuals gender presentation. Gender
is shaped by environment and experience.” Thus, sex is a biological construct
whereas gender is a psychosocial construct. This distinction notwithstanding,
epigenetic research reveals that biological factors often unfold in ways that
are influenced by the environment, and thus can obviate this distinction
between sex and gender. Because it is often not known a priori whether a
male-female difference is sex-based or gender-based or both, in this funding
opportunity announcement sex/gender difference will sometimes be used
generically to refer to male-female differences especially when the biological
and social origins of the differences are unknown or likely involve both. Of
course, the search for those origins is a major focus of this
announcement. In non-human animal research, however, the term sex
difference is the preferred term. Additionally, researchers are urged to
recognize that a sex/gender difference is often a proxy for an unidentified
independent variable(s) and therefore can serve as a research tool. Thus,
finding a sex/gender difference typically should be regarded as a first step in
a search for such variables as their identification will shed light on the
phenomenon under study.

NIDA's
Areas of Research Interest

Areas of research interest include, but are not limited to,
the following:

I.
ETIOLOGY AND MECHANISMS OF DRUG ABUSE: In both animal and human
research, study sex/gender differences in the basic behavioral and biological
mechanisms underlying drug abuse and dependence across the lifespan; and
conduct laboratory, epidemiological, and clinical studies of male-female
differences in the determinants of initiation, progression, and maintenance of
drug use and dependence. Examples include:

Studies of the genetic and epigenetic basis of sex/gender
differences in drug abuse and dependence using a variety of methodologies,
including statistical or epidemiological studies to ascertain heritability;
identification of genetic variants through linkage, linkage disequilibrium, or
association studies; studies of candidate genes using knockout or
over-expression technologies in model organisms; gene expression studies.

Sex/gender differences in the pharmacokinetics and
pharmacodynamics of abused drugs.

Sex/gender differences in the role psychosocial and cognitive
factors in modulating drug effects and drug use.

Preclinical models of social factors and impoverished versus
enriched environments.

Sex/gender differences in the role of current or prior stress,
trauma, violence, victimization and bullying in the development and maintenance
of drug abuse and dependence.

Sex/gender difference in modulation of drug abuse vulnerability
by interactions between the HPA an HPG axes and neurotransmitter systems.

Laboratory studies of sex/gender differences in the role of
tolerance, sensitization, habituation, behavioral alternatives, impulsivity,
delay discounting, stress, learning, memory, and cognition in the development
and maintenance of drug abuse.

Field studies of sex/gender differences in the antecedents and
pathways to drug abuse and dependence, including study of psychosocial and
environmental risk and protective factors associated with initiation,
progression, and maintenance of drug use.

Sex/gender differences in the roles played by the timing of
puberty, the transition to puberty (e.g., onset of menarche), adolescent
physique characteristics, and body image distortion in the onset and
progression of drug abuse.

Sex/gender differences in studies of cumulative accrual of
multiple risks throughout development.

Sex/gender differences in opportunity to use drugs, access to
drugs, patterns of drugs of use and abuse, and factors affecting these
differences.

II.
CONSEQUENCES AND IMPACT: Laboratory (both human and animal), field,
and clinical research aimed at (a) identifying sex/gender differences across
the lifespan in the consequences of drug use, abuse, and addiction following
acute use, chronic use, as well as residual effects following prolonged abstinence,
or (b) examining drug-related consequences that are unique to females.
Examples include:

Sex/gender differences in the effects of abused drugs on various
biological systems including brain structure and function (e.g., effects on
brain reward and stress pathways and effects on neurocognitive circuitry) and
effects on endocrine, immune, cardiovascular, pulmonary and skeletal systems.

Sex/gender differences in the acquisition and transmission of
co-occurring infections (e.g., HIV, HCV, TB, and STDs) among drug users, and
its clinical course and consequences.

Laboratory-based studies of sex/gender differences in the effects
of abused drugs on learning, memory and cognition, and the response to stress.

The effects of drugs of abuse on reproductive behaviors and
maternal and paternal functioning (e.g., parental care, attachment, abuse and
neglect) and differential impact on male and female offspring.

Sex/gender differences in the effect of drug use on the
development and maintenance of social behavior, e.g., play, cooperation,
empathy, conflict, hostility, violence and aggression.

Sex/gender differences in the precipitation and/or exacerbation
of psychiatric disorders following drug use/abuse.

The effects of drugs of abuse on the menstrual/estrous cycle and
on menopause.

The impact of drug abuse during pregnancy on the health, both
physiologically and psychologically, of the mother and her fetus/infant.

Sex/gender differences in offspring prenatally exposed to abused
drugs either via in utero exposure or parental drug use (maternal, paternal or
both) prior to conception; interactions with postnatal factors.

Sex/gender differences in the transgenerational impact of drug
use, including animal model investigations of the biological mechanisms.

Sex/gender differences in the effect of drugs on attainment of
age-appropriate developmental levels, both physiologically and psychologically.

Sex/gender differences in the short- and long-term effects of
exposure to drug-abusing family members (parents, siblings and partners) and
peers.

Assess the differential effectiveness of drug abuse prevention
interventions in males and females and the intervention characteristics and/or
components that account for male-female differences in outcomes.

Identify gender differences in the moderators and mediators of
prevention outcomes.

Develop developmentally-appropriate gender-based universal,
selective and indicated prevention strategies that are guided by etiologic
research findings on sex/gender differences in risk and protective factors and
by sex/gender differences in psychosocial and cognitive development.

In family-based prevention interventions, examine the effect of
gender congruence between the participating parent and child on prevention
outcomes.

Develop gender-based screening and assessment tools aimed at
identifying both risk and protective factors for use at the individual, family
and community levels and in health care settings.

Develop interventions that consider the role of childhood and
adulthood violence and victimization in differentially perpetuating drug abuse
in males and females with attention to environmental, psychosocial and cultural
factors that differentially keep them in the cycle of violence.

Conduct prevention studies on the role of effective
gender-specific communication in media and interpersonal interventions.

Assess the effectiveness of gender-based prevention services and
the factors that affect their availability, adoption, adaptation,
implementation, sustainability, cost benefit, and cost effectiveness.

Develop and test family-oriented treatment approaches that
consider gender-based factors with respect to both parents and children.

Develop and test treatment approaches aimed at the role of
partner drug use.

Identify effective pharmacotherapy use practices for females of
all ages including adolescence and pre-, peri- and postmenopausal women with
consideration for issues such as developmental status, use of contraceptives,
use of hormone therapy, and ovarian hormone status.

Determine best treatment practices for the use of pharmacotherapy
in the treatment of pregnant women and mothers who breastfeed.

Identify gender-specific needs for and use of services ancillary
to drug abuse treatment (e.g., childcare, transportation, housing, skills
training, assertiveness training, and vocational training) and their
differential impact on males and females with respect to access, utilization,
retention, completion, outcomes and cost-benefit.

Identify organizational, management, and treatment financing
practices that impede or facilitate access, utilization, retention and outcomes
for female clients and assess the structure and role of organization in the
development of linkages to other relevant treatment services (e.g., medical
services, prenatal clinics, psychiatric services) to ensure retention and
continuity of care for females, including pregnant and postpartum females.

Develop or enhance and evaluate gender-based instruments for
matching drug-abusing clients to appropriate services, and for identifying,
diagnosing and assessing substance abusers in a variety of treatment settings
especially primary care settings.

Sex/gender-based research to determine the most effective time to
initiate behavioral and pharmacological treatment taking into consideration
menstrual cycle phase and seasonal variations.

V.
HIV/AIDS and RELATED INFECTIOUS DISEASES: Develop and evaluate
sex/gender-based interventions directed at preventing and treating HIV/AIDS and
related infectious diseases among drug using populations and those at risk for
drug use at every age level.

Examine sex/gender differences in the viral, immunologic,
genetic, and drug use factors that may influence susceptibility, recovery and
persistence, and progression of viral diseases associated with drug use.

Examine sex/gender differences in neurocognitive effects of drug
use in HIV/AIDS individuals.

Develop and test gender-based interventions to reduce
gender-based risks of HIV exposure and transmission among drug using
populations. Especially desirable are interventions that also address STIs,
HCV, HBV, and/or risks for TB and other infectious diseases that often co-occur
with HIV or affect acquisition and treatment course.

Examine sex/gender differences in associations among history of
violence and victimization, HIV risk behaviors, and drug abuse.

Examine sex/gender differences in the interactions/effects of
antiretrovirals when used in combination with drugs of abuse and/or medication
to treat drug abuse and/or medication to treat co-occurring disorders.

Develop gender-based strategies (including behavioral, cognitive,
social/ecological, provider-based, setting-based) to improve access, referral,
utilization and adherence to HIV/AIDS medication regimens for drug-abusing
populations both in and out of treatment.

Examine male-female differences in the behavioral dynamics and
drug use-related processes associated with the acquisition and transmission of
HIV and other infectious diseases (e.g., TB, HCV, HBV, STIs), including factors
that influence transitions from non-injection to injection drug use and their
implications for the development of prevention interventions.

Examine the role of drugs of abuse on mother-to-child
transmission of HIV in the presence of highly active antiretroviral therapy
(HAART)

Cross-Cutting
Issues

In addition to the above areas of research on sex/gender
differences and issues unique to women, several research considerations and
topic areas apply to many areas of research. They include, but are not limited
to, the following:

Research that addresses and compares stages of the life cycle,
from preconception, gestation, infancy, childhood, adolescence, adulthood, to
late adulthood.

Research that examines the role of race, ethnicity, culture, and
SES.

Research that examines health disparity issues in drug abuse and
associated infectious diseases.

Research that addresses transgendered populations with special
attention to improving methods for sampling those populations and to their
elevated risk for drug use, and for HIV exposure and transmission.

Research on all drugs of abuse, including the nonmedical use of
prescription drugs, over-the-counter drugs with abuse potential, nicotine, club
drugs, and polydrug use.

Use of a wide range of methodological approaches including
longitudinal studies, secondary data analyses, descriptive and ethnographic
studies, use of and development of novel measurement tools, and interdisciplinary
approaches.

Research that addresses gender-specific recruitment and retention
issues.

Drug
Abuse in Pregnancy and the Post-Partum and Mental Health Comorbidity

See PA-09-174 "Women's Mental Health in Pregnancy and the Postpartum Period (R01)"
for additional description of NIDA’s interest in basic and clinical research
and prevention and treatment interventions on this topic.

Secondary
Data Analyses

Under this announcement, investigators may request funds to
perform secondary data analyses of either their own data sets or other data
sets that are publicly available. For example, NIDA's Clinical Trials
Network Data Share website (http://www.ctndatashare.org)
currently includes HIPAA-de-identified raw data from 23 studies completed by
NIDA's Clinical Trials Network, 20 of which are randomized multi-site clinical
trials. No approval is needed to download the data.

Revision
(formerly competing supplement) Applications

NIDA welcomes applications that request a revision (formerly
competitive supplement) to their active NIDA grant in order to pursue research
on women and sex/gender differences that is relevant to the parent grant, but
which reflects a significant expansion of the scope or research protocol of the
parent grant. The duration of the supplement may not exceed the end date of the
active parent grant. For other requirements and instructions, see http://grants.nih.gov/grants/funding/424/index.htm .

NIAAAs
Areas of Research Interest

Alcohol-related problems including alcohol use disorders
(abuse and dependence) represent a significant public health problem that is
associated with considerable harm to the individual and society.
Epidemiological surveys indicate that, among women, alcohol dependence has not
declined, while alcohol abuse has increased. Despite the fact that alcohol use
is more prevalent among men than women, the genetic and biological mechanisms
for these differences in drinking patterns are not fully known. For example,
women become intoxicated faster than men, achieve higher concentrations of
alcohol in the blood after drinking equivalent amounts of alcohol, and appear
to eliminate alcohol from the blood faster than men. These findings may be due
to various physiological processes and fluctuations in gonadal hormonal levels
that affect the rate of alcohol metabolism making women more susceptible to
alcohols effects. Consequently, women’s health may be more adversely affected
than men’s with the experience of adverse effects that include but are not
limited to intentional or unintentional injuries (e.g., suicide,
traffic-related injuries, falls), acute or chronic health effects (e.g., fetal
alcohol syndrome, increased risk for certain cancers, liver disease, brain
damage, alcohol-induced organ damage), social and/or interpersonal problems
(e.g., sexual assault, physical abuse, violence), and mental health problems
(e.g., mood and anxiety disorders).

Research findings suggest that there are certain high risk
groups (e.g., racial/ethnic) and vulnerable populations (e.g., underage and
younger drinkers) for which more research is needed that examines etiological
issues, complexities of drinking pattern trajectories, genetic risks,
neurobehavioral processes, environmental influences, other drug and/or
psychiatric comorbidity, strategies for early identification, and the
development of effective prevention interventions.

NIAAA is interested in the research areas in this FOA
exemplified in I. Etiology and Mechanisms, II. Consequences and Impact, III.
Prevention and Prevention Services, and V. HIV/AIDS and Related Infectious
Diseases as they relate specifically to alcohol consumption. The research areas
of particular interest to NIAAA include, but are not limited to, the following:

I.
EPIDEMIOLOGY AND PREVENTION:

Studies that evaluate sex differences in vulnerability to alcohol
initiation, lifespan drinking trajectories, transitions over the life course,
intentional/unintentional alcohol-related injuries, including
poisonings/overdose involving alcohol alone or in combination with other drugs,
and risk/protective factors associated with initiation, progression, and
maintenance of alcohol use.

Studies that investigate sex differences in risk and protective
factors for alcohol-related violence and victimization, and determine how these
factors vary and/or interact in different sub-populations (e.g., age,
ethnicity, child or adult victims, etc.) and/or are moderated by factors such
as family history, education, comorbid illicit drug use and/or psychiatric
disorders, and socioeconomic status.

Studies that clarify our understanding of sex differences in how
alcohol use interacts with academic trajectories and social achievement,
impulsivity, negative affect, interpersonal relations, and risk for comorbid
illicit drug use and/or psychiatric comorbidity.

Studies that develop gender-based screening instruments for early
identification of risk for alcohol use disorders, particularly for use with
adolescents in multiple settings (e.g., health care, school, etc.).

Studies that test the effectiveness and cost effectiveness of
developmentally-appropriate gender-based individual, family, and/or
community-based prevention interventions that reduce the risk for the
development of alcohol use disorders, particularly for adolescents and young
adults.

Studies that explore gender differences in being screened for
risking drinking and being offered advice about related harms, and that explore
differences in seeking professional help for alcohol use disorders.

Studies that evaluate the effectiveness of prevention programs to
reduce drinking during pregnancy and risk of fetal alcohol spectrum disorders
(FASD)

Human and animal studies examining the sex differences in
consequences of chronic alcohol use on the brain and cognition, the mechanisms
underlying these differences, and particularly the consequences that are unique
to women.

Documenting male/female variations (patterns) of voluntary
alcohol intake in animal models, including comparisons of males and females in
a variety of drinking paradigms

Establishing the influence of hormones (centrally and/or
peripherally synthesized) on male/female differences in patterns of alcohol
intake and response to alcohol intake.

III. PUBERTAL
AND HORMONAL PROCESSES:

NIAAA has a special interest in sex/gender differences in
drinking patterns that become apparent during puberty, and the mechanisms
underlying these differences. Specifically, we are interested in research that
will increase our understanding of 1) the degree to which hormonal changes at
puberty interact with neurodevelopmental processes to promote sex effects in
alcohol use and misuse, and 2) the effects of adolescent alcohol exposure on
these interactive processes. Research areas of include the following:

Age and sex- related changes in stress responsiveness to alcohol,
and the neurobiological and hormonal mechanisms of these changes.

How pubertal changes in gonadal, neuroactive steroids, and stress
hormones interact within structures in the brain reward circuit to promote sex
differences in alcohol use and misuse that occur during this time.

The effects of hormonal presence or absence during adolescence
(e.g., gonadectomy, hormone replacement studies) on the development of sex
differences in drinking behavior and dependence liability that emerges in late
puberty.

Whether adolescence represents a period of unique sensitivity to
alcohol in modulating development of alcohol abuse through its effects on
hormonal regulation of sex-specific changes in neuronal circuits (including
synapse formation and pruning, glial development), particularly in reward and
emotional circuits.

Secondary
Data Analyses

Under this announcement, investigators may request funds to
perform secondary data analyses of either their own data sets or other data
sets that are publicly available.

Revision
(formerly competing supplement) Applications

NIAAA welcomes applications that request a revision
(formerly competitive supplement) to their active NIAAA grant in order to
pursue research on women and sex/gender differences that is relevant to the
parent grant, but which reflects a significant expansion of the scope or
research protocol of the parent grant. The duration of the supplement may not
exceed the end date of the active parent grant. For other requirements and
instructions, see http://grants.nih.gov/grants/funding/424/index.htm .

Special Considerations

HIV/AIDS Counseling and Testing Policy for the National
Institute on Drug Abuse: In light of recent significant advances in rapid
testing for HIV and in effective treatments for HIV, NIDA has revised its 2001
policy on HIV counseling and testing. NIDA-funded researchers are strongly
encouraged to provide and/or refer research subjects to HIV risk reduction
education and education about the benefits of HIV treatment, counseling and
testing, referral to treatment, and other appropriate interventions to prevent
acquisition and transmission of HIV. This policy applies to all NIDA funded
research conducted domestically or internationally. For more information see http://grants.nih.gov/grants/guide/notice-files/NOT-DA-07-013.html.

National Advisory Council on Drug Abuse Recommended
Guidelines for the Administration of Drugs to Human Subjects: The National
Advisory Council on Drug Abuse (NACDA) recognizes the importance of research
involving the administration of drugs with abuse potential, and dependence or
addiction liability, to human subjects. Potential applicants are encouraged
to obtain and review these recommendations of Council before submitting an
application that will administer compounds to human subjects. The guidelines
are available on NIDA's Web site at http://www.drugabuse.gov/funding/clinical-research/nacda-guidelines-administration-drugs-to-human-subjects

Data Harmonization for Substance Abuse and Addiction via the
PhenX Toolkit: NIDA strongly encourages investigators involved in
human-subjects studies to employ a common set of tools and resources that will
promote the collection of comparable data across studies and to do so by
incorporating the measures from the Core and Specialty collections, which are
available in the Substance Abuse and Addiction Collection of the PhenX Toolkit
(www.phenxtoolkit.org). Please see NOT-DA-12-008 (http://grants.nih.gov/grants/guide/notice-files/NOT-DA-12-008.html)
for further details.

Section II. Award Information

Funding Instrument

Grant: A support mechanism providing money, property, or
both to an eligible entity to carry out an approved project or activity.

Application Types Allowed

New
Resubmission
Revision

The OER
Glossary and the SF424 (R&R) Application Guide provide details on
these application types.

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations
and the submission of a sufficient number of meritorious applications.

Award Budget

The combined budget for direct costs for the two year
project period may not exceed $275,000. No more than $200,000 may be
requested in any single year. Applicants may request direct costs in $25,000
modules, up to the total direct costs limitation of $275,000 for the combined
two-year award period.

Award Project Period

The maximum project period is 2 years.

NIH grants policies as
described in the NIH Grants
Policy Statement will apply to the
applications submitted and awards made in response to this FOA.

Section III. Eligibility
Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

Public/State Controlled Institutions of Higher Education

Private Institutions of Higher Education

The following types of Higher Education Institutions
are always encouraged to apply for NIH support as Public or Private
Institutions of Higher Education:

Applicant organizations must complete and maintain the
following registrations as described in the SF 424 (R&R) Application Guide
to be eligible to apply for or receive an award. All registrations must be
completed prior to the application being submitted. Registration can take 6
weeks or more, so applicants should begin the registration process as soon as
possible. The NIH
Policy on Late Submission of Grant Applications states that failure to
complete registrations in advance of a due date is not a valid reason for a
late submission.

Dun and Bradstreet
Universal Numbering System (DUNS) - All registrations require that
applicants be issued a DUNS number. After obtaining a DUNS number, applicants
can begin both SAM and eRA Commons registrations. The same DUNS number must be
used for all registrations, as well as on the grant application.

System for Award Management (SAM) (formerly CCR) – Applicants must complete and maintain an active registration, which requires renewal at least
annually. The renewal process may require as much time as the
initial registration. SAM registration includes the assignment of a Commercial
and Government Entity (CAGE) Code for domestic organizations which have not
already been assigned a CAGE Code.

eRA Commons - Applicants
must have an active DUNS number and SAM registration in order to complete the
eRA Commons registration. Organizations can register with the eRA Commons as
they are working through their SAM or Grants.gov registration. eRA Commons
requires organizations to identify at least one Signing Official (SO) and at
least one Program Director/Principal Investigator (PD/PI) account in order to
submit an application.

Grants.gov – Applicants
must have an active DUNS number and SAM registration in order to complete the
Grants.gov registration.

Program
Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account and should
work with their organizational officials to either create a new account or to
affiliate an existing account with the applicant organization’s eRA Commons
account. If the PD/PI is also the organizational Signing Official, they must
have two distinct eRA Commons accounts, one for each role. Obtaining an eRA
Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal
Investigator)

Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Program Director(s)/Principal
Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH support.

Applicant organizations may submit more than one application,
provided that each application is scientifically distinct.

NIH will not accept any application that is essentially the
same as one already reviewed within the past thirty-seven months (as described
in the NIH
Grants Policy Statement), except for submission:

To an RFA of an application that was submitted previously as an
investigator-initiated application but not paid;

Of an investigator-initiated application that was originally
submitted to an RFA but not paid; or

Of an application with a changed grant activity code.

Section IV. Application and Submission Information

1. Requesting an
Application Package

Applicants must download the SF424 (R&R) application
package associated with this funding opportunity using the “Apply for Grant
Electronically” button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in
the SF424
(R&R) Application Guide, except where instructed in this funding
opportunity announcement to do otherwise. Conformance to the requirements in
the Application Guide is required and strictly enforced. Applications that are
out of compliance with these instructions may be delayed or not accepted for
review.

All page limitations described in the SF424 Application
Guide and the Table of
Page Limits must be followed.

Required and Optional Components

The forms package associated with this FOA includes all
applicable components, required and optional. Please note that some components
marked optional in the application package are required for submission of
applications for this FOA. Follow all instructions in the SF424 (R&R)
Application Guide to ensure you complete all appropriate “optional” components.

Instructions for Application Submission

The following section supplements the instructions found in
the SF424 (R&R) Application Guide and should be used for preparing an
application to this FOA.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide
must be followed.

R&R or Modular Budget

All instructions in the SF424 (R&R) Application Guide
must be followed.

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) Application Guide
must be followed.

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide
must be followed, with the following additional instructions:

Appendix:
Do not use the Appendix to circumvent page limits. Follow all
instructions for the Appendix as described in the SF424 (R&R) Application
Guide.

Planned Enrollment Report

When conducting clinical research, follow all instructions
for completing Planned Enrollment Reports as described in the SF424 (R&R) Application
Guide.

PHS 398 Cumulative Inclusion Enrollment Report

When conducting clinical research, follow all instructions
for completing Cumulative Inclusion Enrollment Report
as described in the SF424 (R&R) Application Guide.

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies
described in the NIH Grants
Policy Statement, and procedures for foreign institutions described
throughout the SF424 (R&R) Application Guide.

3. Submission Dates and
Times

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications
before the due date to ensure they have time to make any application
corrections that might be necessary for successful submission.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants
across all Federal agencies). Applicants must then complete the submission
process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants
administration. NIH and Grants.gov systems check the application against many
of the application instructions upon submission. Errors must be corrected and a
changed/corrected application must be submitted to Grants.gov on or before the application
due date. If a Changed/Corrected application is submitted after the deadline,
the application will be considered late.

Applicants
are responsible for viewing their application before the due date in the eRA
Commons to ensure accurate and successful submission.

Information on the submission process and a definition of
on-time submission are provided in the SF424 (R&R) Application Guide.

For assistance with your electronic application or for more information on the electronic submission
process, visit Applying
Electronically.

Important
reminders:All PD(s)/PI(s) must include their eRA Commons ID in the
Credential fieldof the Senior/Key Person Profile Component of the
SF424(R&R) Application Package. Failure to register in the Commons
and to include a valid PD/PI Commons ID in the credential field will prevent
the successful submission of an electronic application to NIH. See Section III of this FOA for information on
registration requirements.

The applicant organization must ensure that the DUNS number it provides on the
application is the same number used in the organization’s profile in the eRA
Commons and for the System for Award Management. Additional information may be
found in the SF424 (R&R) Application Guide.

Applicants are required to follow the instructions for
post-submission materials, as described in NOT-OD-13-030.

Section V. Application Review Information

1.
Criteria

Only the review criteria described below will be considered
in the review process. As part of the NIH mission,
all applications submitted to the NIH in support of biomedical and behavioral
research are evaluated for scientific and technical merit through the NIH peer
review system.

For this particular announcement, note the following:

The R21 exploratory/developmental
grant supports investigation of novel scientific ideas or new model systems,
tools, or technologies that have the potential for significant impact on
biomedical or biobehavioral research. An R21 grant application need not have
extensive background material or preliminary information. Accordingly,
reviewers will focus their evaluation on the conceptual framework, the level of
innovation, and the potential to significantly advance our knowledge or
understanding. Appropriate justification for the proposed work can be provided
through literature citations, data from other sources, or, when available, from
investigator-generated data. Preliminary data are not required for R21
applications; however, they may be included if available.

Overall Impact

Reviewers will provide an overall impact score to reflect
their assessment of the likelihood for the project to exert a sustained,
powerful influence on the research field(s) involved, in consideration of the
following review criteria and additional review criteria (as applicable for the
project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in
the determination of scientific merit, and give a separate score for each. An
application does not need to be strong in all categories to be judged likely to
have major scientific impact. For example, a project that by its nature is not
innovative may be essential to advance a field.

Significance

Does the project address an important problem or a
critical barrier to progress in the field? If the aims of the project are
achieved, how will scientific knowledge, technical capability, and/or clinical
practice be improved? How will successful completion of the aims change the concepts,
methods, technologies, treatments, services, or preventative interventions that
drive this field?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other
researchers well suited to the project? If Early Stage Investigators or New
Investigators, or in the early stages of independent careers, do they have
appropriate experience and training? If established, have they demonstrated an
ongoing record of accomplishments that have advanced their field(s)? If the
project is collaborative or multi-PD/PI, do the investigators have
complementary and integrated expertise; are their leadership approach,
governance and organizational structure appropriate for the project?

Innovation

Does the application challenge and seek to shift
current research or clinical practice paradigms by utilizing novel theoretical
concepts, approaches or methodologies, instrumentation, or interventions? Are
the concepts, approaches or methodologies, instrumentation, or interventions
novel to one field of research or novel in a broad sense? Is a refinement,
improvement, or new application of theoretical concepts, approaches or
methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project?
Are potential problems, alternative strategies, and benchmarks for success
presented? If the project is in the early stages of development, will the
strategy establish feasibility and will particularly risky aspects be
managed?

If the project involves human subjects and/or NIH-defined clinical research,
are the plans to address 1) the protection of human subjects from research
risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender,
race, and ethnicity, as well as the inclusion or exclusion of children,
justified in terms of the scientific goals and research strategy proposed?

Environment

Will the scientific environment in which the work
will be done contribute to the probability of success? Are the institutional
support, equipment and other physical resources available to the investigators
adequate for the project proposed? Will the project benefit from unique
features of the scientific environment, subject populations, or collaborative
arrangements?

Additional Review Criteria

As applicable for the project proposed, reviewers will
evaluate the following additional items while determining scientific and
technical merit, and in providing an overall impact score, but will not give
separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does
not involve one of the six categories of research that are exempt under 45 CFR
Part 46, the committee will evaluate the justification for involvement of human
subjects and the proposed protections from research risk relating to their
participation according to the following five review criteria: 1) risk to
subjects, 2) adequacy of protection against risks, 3) potential benefits to the
subjects and others, 4) importance of the knowledge to be gained, and 5) data
and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or
more of the six categories of research that are exempt under 45 CFR Part 46,
the committee will evaluate: 1) the justification for the exemption, 2) human
subjects involvement and characteristics, and 3) sources of materials. For
additional information on review of the Human Subjects section, please refer to
the Guidelines
for the Review of Human Subjects.

Inclusion of Women, Minorities, and
Children

When the proposed project involves human subjects
and/or NIH-defined clinical research, the committee will evaluate the proposed
plans for the inclusion (or exclusion) of individuals on the basis of
sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of
children to determine if it is justified in terms of the scientific goals and
research strategy proposed. For additional information on review of the
Inclusion section, please refer to the Guidelines
for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live
vertebrate animals as part of the scientific assessment according to the
following five points: 1) proposed use of the animals, and species, strains,
ages, sex, and numbers to be used; 2) justifications for the use of animals and
for the appropriateness of the species and numbers proposed; 3) adequacy of
veterinary care; 4) procedures for limiting discomfort, distress, pain and
injury to that which is unavoidable in the conduct of scientifically sound
research including the use of analgesic, anesthetic, and tranquilizing drugs
and/or comfortable restraining devices; and 5) methods of euthanasia and reason
for selection if not consistent with the AVMA Guidelines on Euthanasia. For
additional information on review of the Vertebrate Animals section, please
refer to the Worksheet
for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures
proposed are potentially hazardous to research personnel and/or the
environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

For Resubmissions, the committee will evaluate the
application as now presented, taking into consideration the responses to
comments from the previous scientific review group and changes made to the
project.

Renewals

Not Applicable

Revisions

For Revisions, the committee will consider the
appropriateness of the proposed expansion of the scope of the project. If the
Revision application relates to a specific line of investigation presented in
the original application that was not recommended for approval by the committee,
then the committee will consider whether the responses to comments from the
previous scientific review group are adequate and whether substantial changes
are clearly evident.

Additional Review Considerations

As applicable for the project proposed, reviewers will
consider each of the following items, but will not give scores for these items,
and should not consider them in providing an overall impact score.

Applications from Foreign
Organizations

Reviewers will assess whether the project presents
special opportunities for furthering research programs through the use of
unusual talent, resources, populations, or environmental conditions that exist
in other countries and either are not readily available in the United States or
augment existing U.S. resources.

Select Agent Research

Reviewers will assess the information provided in
this section of the application, including 1) the Select Agent(s) to be used in
the proposed research, 2) the registration status of all entities where Select
Agent(s) will be used, 3) the procedures that will be used to monitor possession
use and transfer of Select Agent(s), and 4) plans for appropriate biosafety,
biocontainment, and security of the Select Agent(s).

Reviewers will consider whether the budget and the
requested period of support are fully justified and reasonable in relation to
the proposed research.

2. Review and Selection
Process

Applications will be evaluated for scientific and technical
merit by (an) appropriate Scientific Review Group(s), in accordance with NIH peer
review policy and procedures, using the stated review
criteria. Assignment to a Scientific Review Group will be shown in the eRA
Commons.

As part of the scientific peer review, all applications:

May undergo a selection process in which only those applications
deemed to have the highest scientific and technical merit (generally the top
half of applications under review) will be discussed and assigned an overall impact
score.

Will receive a written critique.

Applications will be assigned on the basis of established
PHS referral guidelines to the appropriate NIH Institute or Center. Applications
will compete for available funds with all other recommended applications. Following
initial peer review, recommended applications will receive a second level of
review by the appropriate national Advisory Council or Board. The following
will be considered in making funding decisions:

Scientific and technical merit of the proposed project as determined
by scientific peer review.

Availability of funds.

Relevance of the proposed project to program priorities.

3. Anticipated Announcement
and Award Dates

After the peer review of the application is completed, the
PD/PI will be able to access his or her Summary Statement (written critique)
via the eRA
Commons.

If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as described
in the NIH
Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided
to the applicant organization for successful applications. The NoA signed by
the grants management officer is the authorizing document and will be sent via
email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award costs.

When multiple years are involved, awardees will be required
to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR)
and financial statements as required in the NIH Grants
Policy Statement.

A final progress report, invention
statement, and the expenditure data portion of the Federal Financial Report are
required for closeout of an award, as described in the NIH Grants
Policy Statement.

The Federal Funding Accountability and Transparency Act of
2006 (Transparency Act), includes a requirement for awardees of Federal grants
to report information about first-tier subawards and executive compensation
under Federal assistance awards issued in FY2011 or later. All awardees of
applicable NIH grants and cooperative agreements are required to report to
the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants
Policy Statement for additional information on this reporting
requirement.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity
and welcome the opportunity to answer questions from potential applicants.

Awards are made under the authorization of Sections 301 and
405 of the Public Health Service Act as amended (42 USC 241 and 284) and under
Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.